21 results on '"Loch M"'
Search Results
2. HIPOPARATIREOIDISMO IDIOPÁTICO COM CALCIFICAÇÕES CEREBRAIS MÚLTIPLAS
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WASKIEWICZ, V. V., primary, BARBOSA, M. E. M., additional, SOUSA, H. S., additional, ALEXANDRE, G. P., additional, LOCH, M. A. L., additional, and GENTILINI NETO, GENTILINI NETO, additional
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- 2022
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3. 123 - A rare form of germ cell tumor: testicular extragonadal choriocarcinoma
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Pham, C, Germain, M, Loch, M, Sanne, S, and Garcia, A
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- 2024
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4. Phase Ib/IIa study assessing the safety and efficacy of adding AL3818 (anlotinib) to standard platinum-based chemotherapy in subjects with recurrent or metastatic endometrial, ovarian or cervical carcinoma
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Miller, D., primary, Miller, D.S., additional, Cheung, E., additional, Huang, M., additional, Schlumbrecht, M., additional, Garcia, A., additional, Loch, M., additional, Jernigan, A., additional, Li, Z., additional, Chen, M., additional, and Chen, J., additional
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- 2019
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5. Abstract P5-08-30: Utilization of oncotype DX for breast cancer in different facility types in Louisiana
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Loch, M, primary, Li, X, additional, Mumphrey, B, additional, Garcia, A, additional, and Wu, X-C, additional
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- 2017
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6. 1033P - Phase Ib/IIa study assessing the safety and efficacy of adding AL3818 (anlotinib) to standard platinum-based chemotherapy in subjects with recurrent or metastatic endometrial, ovarian or cervical carcinoma
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Miller, D., Miller, D.S., Cheung, E., Huang, M., Schlumbrecht, M., Garcia, A., Loch, M., Jernigan, A., Li, Z., Chen, M., and Chen, J.
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- 2019
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7. (054) OPTIMIZING INTERNET-BASED PSYCHOSOCIAL INTERVENTION FOR BREAST CANCER-RELATED SEXUAL MORBIDITY: PROTOCOL FOR A FACTORIAL TRIAL.
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Shaffer, K, Reese, J, Dressler, E V, Cohn, W, Glazer, J V, Frederick, C, Showalter, S, Clayton, A H, Loch, M, Danhauer, S C, Collins, L, Weaver, K E, Lesser, G J, and Ritterband, L
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PSYCHO-oncology , *DYSPAREUNIA , *HEALTH care teams , *EMPLOYEE ownership , *VAGINAL dryness , *LUST , *BREAST cancer , *GENITOURINARY diseases , *CANCER fatigue - Abstract
Introduction: Although 3 in 4 breast cancer survivors report significant sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to breast cancer survivors via the Internet could overcome many of the barriers to in-person interactions, including limited availability of resources and stigma. Prior research on telehealth interventions for breast cancer survivors' sexual health has limitations. First, survivors continue to endorse time burden as a leading reason for declining telehealth sexual health interventions. Second, prior trial designs have not been able to determine which intervention components work best for which survivors. This knowledge is crucial to refine and personalize sexual health care for survivors. Objective: Use the Multiphase Optimization Strategy (MOST) methodological framework to achieve the following aims: (1) develop an Internet intervention for breast cancer-related sexual health that is optimized for greatest impact; and (2) determine how intervention components work (i.e., mediators) and for whom they work best (i.e., moderators). Methods: 320 partnered, post-treatment female breast cancer survivors who endorse at least one bothersome sexual symptom (i.e., pain with sex, vaginal dryness, low sexual desire, difficulty with orgasm) related to their breast cancer treatment will be enrolled. Recruitment will be conducted via a US-national community oncology research program representing more than 1,000 individual practice locations. In this factorial trial, participants will be randomized to receive a combination of 4 intervention components: psychoeducation about cancer-related sexual morbidity, training for communication with their health care team, training for communication with their partners, and intimacy promotion skills training. These components were selected as they are supported by our intervention research, are consistent with survivorship guidelines, and align with survivors' preferences found in our qualitative research. Components will be implemented using a robust Internet intervention platform with tailoring and highly-engaging elements like animation, video, and automated email prompts. Survivors will complete assessments at baseline (pre-randomization) and 3- and 6-month post-assessments. First, the impact of intervention components on survivors' sexual distress (Female Sexual Distress Scale-Desire, Arousal, Orgasm) and sexual functioning (Female Sexual Function Inventory) will be tested. Next, a select set of mediators (i.e., sexual functioning knowledge, sexual communication self-efficacy with clinicians and partner, emotional intimacy with partner) and moderators (i.e., menopausal status, adjuvant endocrine therapy use, psychological distress, relationship duration and satisfaction) will be evaluated. Results: Institutional review board approvals are in progress, with clinical trial registration to follow. Data collection is anticipated to begin in Spring 2024 and be completed in 2027. Conclusions: Findings from this trial will accelerate the development of more effective sexual health interventions for breast cancer survivors by determining how intervention components work and for whom various components work best. By identifying the combination of intervention components likely to provide breast cancer survivors the greatest sexual health benefit for the least burden, this study will result in the first Internet intervention optimized for maximum impact for the undertreated, prevalent, and distressing problem of breast cancer-related sexual morbidity. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: AHC: grants from Janssen, Relmada Therapeutics, Inc., and Sage Therapeutics; personal fees from Acadia, Alkermes, Allergan, AMAG Pharmaceuticals, Inc., Fabre-Kramer, Ovoca Bio plc, Pure Tech Health, Sage Therapeutics, Takeda/Lundbeck, WCG MedAvante-ProPhase, Ballantine Books/Random House, Changes in Sexual Functioning Questionnaire, Guilford Publications; personal fees and other from S1 Biopharma; and other from Euthymics and Mediflix LLC. GL: consultant or research affiliation with Agios Pharmaceuticals, Inc; Denovo Biopharma; IN8bio; Incyte Corporation; Novocure Inc.; oblato; ONO Pharma; Sumitomo Dainippon Pharma Co., Ltd. LR: financial and/or business interest in BeHealth Solutions and is a consultant to Mahana Therapeutics. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Associations of Neonatal Dairy Calf Faecal Microbiota with Inflammatory Markers and Future Performance.
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Loch M, Dorbek-Sundström E, Husso A, Pessa-Morikawa T, Niine T, Kaart T, Mõtus K, Niku M, and Orro T
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After birth, the immune system is challenged by numerous elements of the extrauterine environment, reflected in fluctuations of inflammatory markers. The concentrations of these markers in the first month of life are associated with the future performance of dairy youngstock. It is thought that bacterial genera colonizing the calf intestinal tract can cause inflammation and thus affect their host's performance via immunomodulation. This study explored how the faecal microbiota of newborn dairy calves were related to inflammatory markers during the first three weeks of life, and if the abundance of specific genera was associated with first-lactation performance. Ninety-five female Holstein calves were studied. Once a week, serum and faecal samples were collected, serum concentrations of serum amyloid A, haptoglobin, tumour necrosis factor-α, and interleukin-6 were measured, and faecal microbiota composition was examined by 16S rRNA gene amplicon sequencing. Faecal Gallibacterium abundance in the first week of age and Collinsella abundance in the second week were negatively associated with inflammatory response as well as with calving-conception interval. Peptostreptococcus abundance in the second week of life was positively associated with inflammatory response and calving-conception interval, and negatively with average daily weight gain. In the third week, Dorea abundance was positively, Bilophila abundance was negatively associated with inflammatory response, and both genera were negatively associated with age at first calving. These bacterial genera may be able to influence the inflammatory response and through this, possibly the future performance of the dairy heifer. Deciphering such microbiota-host interactions can help improve calf management to benefit production and welfare.
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- 2024
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9. Factorial Trial to Optimize an Internet-Delivered Intervention for Sexual Health After Breast Cancer: Protocol for the WF-2202 Sexual Health and Intimacy Enhancement (SHINE) Trial.
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Shaffer KM, Reese JB, Dressler EV, Glazer JV, Cohn W, Showalter SL, Clayton AH, Danhauer SC, Loch M, Kadi M, Smith C, Weaver KE, Lesser GJ, and Ritterband LM
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- Humans, Female, Adult, Internet, Middle Aged, Breast Neoplasms psychology, Breast Neoplasms therapy, Sexual Health, Internet-Based Intervention, Cancer Survivors psychology
- Abstract
Background: Although most survivors of breast cancer report substantial sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to survivors of breast cancer via the internet could overcome many of the barriers to in-person treatment. Even when delivered remotely, survivor time constraints remain a leading barrier to sexual health intervention uptake., Objective: Guided by the multiphase optimization strategy methodological framework, the primary objective of this study is to identify the most efficient internet-delivered sexual health intervention package that is expected to provide survivors of breast cancer the greatest benefit with the fewest (and least-intensive) intervention components. This study aims to determine how intervention components work (mediators) and for whom they work best (moderators)., Methods: Partnered, posttreatment adult female survivors of breast cancer (N=320) experiencing at least 1 bothersome sexual symptom (ie, pain with sex, vaginal dryness, low sexual desire, and difficulty with orgasm) related to their breast cancer treatment will be enrolled. Clinic-based recruitment will be conducted via the Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participants will be randomly assigned to 1 of 16 combinations of four intervention components with two levels each in this factorial trial: (1) psychoeducation about cancer-related sexual morbidity (receive either enhanced vs standard versions); (2) communication skills training for discussing concerns with health care providers (received vs not received); (3) communication skills training for discussing concerns with a partner (received vs not received); and (4) intimacy promotion skills training (received vs not received). Cores will be fully automated and implemented using a robust internet intervention platform with highly engaging elements such as animation, video, and automated email prompts. Survivors will complete web-based assessments at baseline (prerandomization time point) and again at 12 and 24 weeks later. The primary study aim will be achieved through a decision-making process based on systematically evaluating the main and interaction effects of components on sexual distress (Female Sexual Distress Scale-Desire, Arousal, Orgasm) and sexual functioning (Female Sexual Function Index) using a generalized linear model approach to ANOVA with effect coding. Mediation analyses will be conducted through a structural equation modeling approach, and moderation analyses will be conducted by extending the generalized linear model to include interaction effects., Results: This protocol has been reviewed and approved by the National Cancer Institute Central Institutional Review Board. Data collection is planned to begin in March 2024 and conclude in 2027., Conclusions: By identifying the combination of the fewest and least-intensive intervention components likely to provide survivors of breast cancer the greatest sexual health benefit, this study will result in the first internet intervention that is optimized for maximum impact on the undertreated, prevalent, and distressing problem of breast cancer-related sexual morbidity., Trial Registration: ClinicalTrials.gov NCT06216574; https://clinicaltrials.gov/study/NCT06216574., International Registered Report Identifier (irrid): PRR1-10.2196/57781., (©Kelly M Shaffer, Jennifer Barsky Reese, Emily V Dressler, Jillian V Glazer, Wendy Cohn, Shayna L Showalter, Anita H Clayton, Suzanne C Danhauer, Michelle Loch, Mai Kadi, Caleigh Smith, Kathryn E Weaver, Glenn J Lesser, Lee M Ritterband. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 19.08.2024.)
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- 2024
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10. Association of clinical respiratory disease signs and lower respiratory tract bacterial pathogens with systemic inflammatory response in preweaning dairy calves.
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Kaura R, Dorbek-Kolin E, Loch M, Viidu DA, Orro T, and Mõtus K
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- Animals, Cattle, Cross-Sectional Studies, Respiratory Tract Diseases veterinary, Respiratory Tract Diseases microbiology, Inflammation veterinary, Estonia, Female, Fibrinogen analysis, Cattle Diseases microbiology
- Abstract
This study investigated the potential associations between 3 acute phase proteins (APP)-haptoglobin, serum amyloid A-and fibrinogen, clinical signs of respiratory disease, and the presence of bacterial pathogens in the lower respiratory tract (LRT) of preweaning dairy calves. This cross-sectional study included 150 preweaning calves (2-86 d old) from 15 large dairy herds in Estonia. Tracheobronchial lavage, blood, and fecal samples were collected from 5 calves showing clinical signs indicative of LRT disease, and samples from 5 calves without clinical signs of LRT disease per herd. All samples collected from these calves were analyzed for concentrations of systemic APP, LRT bacteria, and intestinal pathogens. Heifer blood and bulk tank milk samples were collected for the detection of disease-specific antibodies against bovine herpesvirus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, and Mycoplasma bovis. Mixed-effects linear regression models were used to analyze the associations of clinical respiratory disease signs and LRT bacteria with APP. Increased plasma fibrinogen concentrations in calves were associated with higher rectal temperature (>39.5°C), increased respiratory rate (>50 breaths/min), and coughing. Increased serum amyloid A concentrations were associated with higher rectal temperature (>39.5°C) and respiratory rate between 40 and 50 breaths/min. Calves with the presence of fecal Cryptosporidium spp. and rectal temperature of 39°C and above had increased serum haptoglobin concentrations. Increased fibrinogen concentrations were associated with the presence of Pasteurella multocida in the calf LRT, whereas increased concentrations of fibrinogen and serum amyloid A were associated with the presence of Trueperella pyogenes. In conclusion, APP showed variable associations with clinical signs of respiratory disease and LRT bacteria. Plasma fibrinogen concentration could be used as a complementary calf-side test to assess systemic inflammation caused by LRT bacteria such as Pasteurella multocida and Trueperella pyogenes in preweaning dairy calves., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)
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- 2024
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11. Associations of neonatal acute phase response with first lactation performance in dairy cows.
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Loch M, Niine T, Dorbek-Kolin E, Peetsalu K, and Orro T
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- Female, Animals, Cattle, Interleukin-6, Acute-Phase Reaction veterinary, Tumor Necrosis Factor-alpha, Cytokines, Acute-Phase Proteins, Haptoglobins, Lactation, Serum Amyloid A Protein, Cryptosporidiosis, Cryptosporidium, Cattle Diseases
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During the first 3 wk of life, the immune system of newborn ruminants starts to work, as indicated by fluctuations in the concentrations of proinflammatory cytokines and acute phase proteins (APP). They have been shown to be markers for short and long-term weight gain in ruminants. This observational study investigated these proteins as possible indicators of first lactation performance of dairy cows. A total of 117 dairy calves from a single farm were enrolled in the study. Serum and fecal samples were taken once a week for the first 3 wk of life. Cryptosporidium spp. infection and its treatment were monitored and accounted for in statistical analysis. The concentrations of the APP serum amyloid A (SAA) and haptoglobin (Hp), and the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were analyzed in serum. After the first lactation, health and performance data of the cows were retrieved, and associations between APP and cytokine concentrations with first lactation outcomes were investigated through linear and logistic regression. This study found a negative association between the concentration of Hp in the second week of life and average daily weight gain at one year. The SAA concentration measured during the second and third weeks of life was positively associated with age at first calving. IL-6, SAA, and Hp measured in the second week of life were positively associated with calving to conception interval. The concentrations of IL-6 and TNF-α during the first week of life were associated with higher odds of reproductive issues during the first lactation period. These markers can be used to help understand underlying processes that influence animal health and production. In conclusion, inflammatory responses during the first week of life are related to reproductive success, whereas the second and third weeks of life seem to influence the future productive performance in dairy cows., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)
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- 2023
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12. The Use of Eculizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in an Academic Hematology Center.
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Thomas K, Ananthula A, Lopez-Flores R, Toro AD, Chapple AG, and Loch M
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- Aged, United States, Humans, Retrospective Studies, Medicare, Atypical Hemolytic Uremic Syndrome drug therapy, Atypical Hemolytic Uremic Syndrome genetics, Hematology
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Introduction Eculizumab is a complement inhibitor used in treating atypical hemolytic uremic syndrome (aHUS). This study showcases patient demographics, clinical and laboratory results of these patients, and overall outcomes of patients with aHUS treated with eculizumab. Methods The authors conducted a retrospective case study including 9 patients who received at least 1 dose of eculizumab for treating aHUS. A linear mixed effects model was used with random effects for each patient and fixed effects for eculizumab and time since admission. A p value < 0.05 was significant. Results Nine patients were treated with eculizumab for aHUS. Most patients were Black (n = 5) with either Medicare or Medicaid (n = 5). Genetic mutations were tested for in 5 patients. There were significant decreases in lactate dehydrogenase (LD, p = 0.029) and creatinine (Cr, p = 0.012) when on treatment. No significance was found in hemoglobin (p = 0.258) or platelets (p = 0.569). Treatment was stopped in 7 patients, of which 3 had no evidence of disease relapse. The only adverse event was severe thrombocytopenia (n = 1). Discussion This multicase study is the first of its kind in which most patients are Black, showing that there is a lack of research of this kind, especially on genetic mutations. Most of our patients did not have private insurance or had Medicaid/Medicare. There was a 246.5-day median duration of treatment. There was low risk of adverse events. Conclusion This case series elucidates the effective use of eculizumab for atypical hemolytic uremic syndromein a diverse patient population and emphasizes the need for more research in this area., Competing Interests: Conflicts of InterestNone declared
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- 2023
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13. Faecal microbiota in two-week-old female dairy calves during acute cryptosporidiosis outbreak - Association with systemic inflammatory response.
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Dorbek-Kolin E, Husso A, Niku M, Loch M, Pessa-Morikawa T, Niine T, Kaart T, Iivanainen A, and Orro T
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- Animals, Cattle, Disease Outbreaks, Feces microbiology, Female, Haptoglobins, Oocysts, Prevalence, Serum Amyloid A Protein, Systemic Inflammatory Response Syndrome veterinary, Weight Gain, Cattle Diseases epidemiology, Cryptosporidiosis epidemiology, Cryptosporidium genetics, Microbiota
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In the present study, relationships between the intestinal microbiota and innate immunity response, acute cryptosporidiosis, and weight gain in female dairy calves were investigated. A total of 112 calves born during a natural outbreak of cryptosporidiosis on one dairy farm was included in the study. Microbiota composition was analysed by means of 16S ribosomal RNA gene amplicon sequencing from faecal samples collected during the second week of life, while the status of Cryptosporidium spp. infection was determined using immunofluorescence. Serum samples from the second week of life were colourimetrically analysed for the following markers of acute inflammation: acute-phase proteins (serum amyloid A and haptoglobin) and pro-inflammatory cytokines (interleukin-1 beta, interleukin-6, and tumour necrosis factor-alpha). Statistical analyses were performed using random forest analysis, variance-partitioning, and negative binomial regression. The faecal microbiota of the two-week old calves was composed of the phyla Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, and Actinobacteria (in order of decreasing abundance). Microbial diversity, measured in terms of the Shannon index, increased with the age of the calves and decreased if a high count of Cryptosporidium spp. oocysts was found in the faeces. Fusobacterium was positively associated with Cryptosporidium spp. oocyst count and serum amyloid A concentration. Peptostreptococcus was positively associated with haptoglobin and serum amyloid A concentrations, and negatively associated with average daily weight gain at 9 months of age. The markers of innate immunity, in combination with age, explained 6% of the microbial variation. These results suggest that some components of the intestinal microbiota may have a long-lasting negative effect on animal growth through the stimulation of the systemic innate immune response., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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14. Effect of colostrum on the acute-phase response in neonatal dairy calves.
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Peetsalu K, Niine T, Loch M, Dorbek-Kolin E, Tummeleht L, and Orro T
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- Acute-Phase Proteins metabolism, Acute-Phase Reaction metabolism, Acute-Phase Reaction veterinary, Animals, Animals, Newborn, Cattle, Cytokines metabolism, Female, Haptoglobins metabolism, Interleukin-6 metabolism, Mammals metabolism, Pregnancy, Serum Amyloid A Protein metabolism, Tumor Necrosis Factor-alpha metabolism, Weight Gain, Cattle Diseases metabolism, Colostrum
- Abstract
The core part of the mammal innate immune system is the acute-phase response (APR), during which acute-phase proteins (APP) are synthesized. Colostrum contains immunomodulating factors such as proinflammatory cytokines and APP in large quantities. We looked at proinflammatory cytokines [IL-1β, IL-6, and tumor necrosis factor-α (TNF-α)] and APP [serum amyloid A (SAA) and haptoglobin (Hp)] in colostrum and in calves' serum. The aim of this study was to evaluate the effects of colostrum on the calves' systemic APR and the associations of the calves' serum APR with short- and long-term weight gain (at the age of 1, 3, and 9 mo). A total of 143 female dairy calves were studied during their first 3 wk of life. The calves were separated from their mothers immediately after birth and bottle-fed 3 L of quality-controlled colostrum once within 2 h after birth. Serum samples were collected once a week during the first 3 wk of life (a total of 1-3 samples per calf). Mean sampling age (±standard deviation) was 4.3 (±2.0) d in the first week, 11.0 (±2.0) d in the second week, and 18.0 (±2.0) d in the third week. Linear regression models were used to study associations of colostrum APP and cytokine concentration with serum APR markers and for studying associations of colostrum and serum APR markers with calves' average daily weight gain (ADWG). Mixed linear regression models were used to compare serum concentrations of APR markers by study weeks. The colostrum IL-6 concentrations were positively associated with serum IL-6 in the first 3 wk of life. Colostrum IL-1β was positively associated with calves' serum IL-1β during the first week of life, and colostrum TNF-α was positively associated with calves' serum TNF-α during the first 2 wk of life. Serum IL-1β concentrations differed over the 3 wk, being the highest during the first week and the lowest during the second week. For IL-6, the concentration during the first week was the highest, and for TNF-α, a steady decline in the concentration was observed. Serum SAA concentrations were elevated during the first 2 wk of life and subsequently declined during the third week. Albumin concentrations were lowest in the first week, whereas Hp concentrations were highest during the second week. Serum concentrations of SAA, Hp, IL-6, and TNF-α during the second week were negatively associated with ADWG at 9 mo of age. The SAA concentrations during the third week of age had a negative association with 9-mo ADWG. Serum Hp concentrations in the third week were negatively associated with 3-mo ADWG. The results of our study suggest that colostrum cytokines influence calf serum cytokine concentrations. Thus, they influence the newborn calves' adaptation to the environment and the development of their immune system. Factors that activate an APR during the second and third week of life have a long-term influence on calves' development., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)
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- 2022
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15. Identification of Germline Non-coding Deletions in XIAP Gene Causing XIAP Deficiency Reveals a Key Promoter Sequence.
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Sbihi Z, Tanita K, Bachelet C, Bole C, Jabot-Hanin F, Tores F, Le Loch M, Khodr R, Hoshino A, Lenoir C, Oleastro M, Villa M, Spossito L, Prieto E, Danielian S, Brunet E, Picard C, Taga T, Abdrabou SSMA, Isoda T, Yamada M, Palma A, Kanegane H, and Latour S
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- Germ Cells metabolism, Humans, Male, X-Linked Inhibitor of Apoptosis Protein, Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked genetics, Lymphoproliferative Disorders diagnosis, Lymphoproliferative Disorders genetics, Lymphoproliferative Disorders metabolism
- Abstract
Purpose: X-linked inhibitor of apoptosis protein (XIAP) deficiency, also known as the X-linked lymphoproliferative syndrome of type 2 (XLP-2), is a rare immunodeficiency characterized by recurrent hemophagocytic lymphohistiocytosis, splenomegaly, and inflammatory bowel disease. Variants in XIAP including missense, non-sense, frameshift, and deletions of coding exons have been reported to cause XIAP deficiency. We studied three young boys with immunodeficiency displaying XLP-2-like clinical features. No genetic variation in the coding exons of XIAP was identified by whole-exome sequencing (WES), although the patients exhibited a complete loss of XIAP expression., Methods: Targeted next-generation sequencing (NGS) of the entire locus of XIAP was performed on DNA samples from the three patients. Molecular investigations were assessed by gene reporter expression assays in HEK cells and CRISPR-Cas9 genome editing in primary T cells., Results: NGS of XIAP identified three distinct non-coding deletions in the patients that were predicted to be driven by repetitive DNA sequences. These deletions share a common region of 839 bp that encompassed the first non-coding exon of XIAP and contained regulatory elements and marks specific of an active promoter. Moreover, we showed that among the 839 bp, the exon was transcriptionally active. Finally, deletion of the exon by CRISPR-Cas9 in primary cells reduced XIAP protein expression., Conclusions: These results identify a key promoter sequence contained in the first non-coding exon of XIAP. Importantly, this study highlights that sequencing of the non-coding exons that are not currently captured by WES should be considered in the genetic diagnosis when no variation is found in coding exons., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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16. Exploring the π-System of the (Aza-)BOIMPY Scaffold: Electron-Rich Pyrrole Moieties Working in Concert with Electron-Depleted Meso-Positions.
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Patalag LJ, Loch M, Jones PG, and Werz DB
- Abstract
The recently introduced (Aza-)BOIMPY scaffold (bis(borondifluoride)-8-imidazodipyrromethene) is equipped with electron-rich β-alkoxy/α-aryl-substituted pyrrole moieties to saturate the highly electron-depleted, benzimidazole- and tetrazole-bearing meso-positions of the (Aza-)BOIMPY core. The established push-pull system gives rise to a series of compact, red- and near-infrared absorbing dyes and fluorophores with inverted high polarity compared to the native borondipyrromethene motif. The extent of conjugation of the pyrrolic α-aryl fragments with the dipyrrin core is studied by density functional theory (DFT) computations and correlated with observed red-shifts, vibronic progressions, and emission properties. In the course of the stepwise red-shift induced by more compact, electron-rich α-aryl groups, quantum yields of fluorescence decrease dramatically despite mitigated excited state relaxations. Time-dependent DFT (TDDFT) computations reveal the modes of geometrical relaxations upon excitation and their influence on fluorescence quantum yields; they also provide background information for further structural refinements.
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- 2019
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17. Palladium-catalyzed enantioselective alkenylation of alkenylbenzene derivatives.
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Chen ZM, Liu J, Guo JY, Loch M, DeLuca RJ, and Sigman MS
- Abstract
A regioselective and enantioselective palladium-catalyzed relay Heck alkenylation of alkenylbenzene derivatives to construct remote stereocenters is disclosed. Various β-substituted styrenes were readily obtained in moderate yields with good to excellent levels of enantioselectivity. This strategy provides rapid access to enantioenriched δ, ε, ζ, and η-alkenyl aryl compounds from simple starting materials. Mechanistic studies suggest that termination of the relay reaction is controlled by affinity of the arene for the Pd complex during migration., (This journal is © The Royal Society of Chemistry 2019.)
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- 2019
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18. Population-Based Study on Cancer Subtypes, Guideline-Concordant Adjuvant Therapy, and Survival Among Women With Stage I-III Breast Cancer.
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Hsieh MC, Zhang L, Wu XC, Davidson MB, Loch M, and Chen VW
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- Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols standards, Biomarkers, Tumor analysis, Breast pathology, Breast surgery, Breast Neoplasms mortality, Breast Neoplasms pathology, Chemotherapy, Adjuvant standards, Chemotherapy, Adjuvant statistics & numerical data, Clinical Decision-Making, Female, Follow-Up Studies, Guideline Adherence standards, Guideline Adherence statistics & numerical data, Humans, Kaplan-Meier Estimate, Mastectomy, Middle Aged, Neoplasm Staging, Practice Guidelines as Topic, Receptor, ErbB-2 analysis, Receptor, ErbB-2 metabolism, Receptors, Estrogen analysis, Receptors, Estrogen metabolism, Receptors, Progesterone analysis, Receptors, Progesterone metabolism, Registries statistics & numerical data, Socioeconomic Factors, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor metabolism, Breast Neoplasms therapy
- Abstract
Background: Breast cancer subtype is a key determinant in treatment decision-making, and also effects survival outcome. In this population-based study, in-depth analyses were performed to examine the impact that breast cancer subtype and receipt of guideline-concordant adjuvant systemic therapy (AST) have on survival using a population-based cancer registry's data., Methods: Women aged ≥20 years with microscopically confirmed stage I-III breast cancer diagnosed in 2011 were identified from the Louisiana Tumor Registry. Breast cancer subtypes were categorized based on hormone receptor (HR) and HER2 status. Guideline-concordant treatment was defined using the NCCN Guidelines for Breast Cancer. Logistic regression was applied to identify factors associated with guideline-concordant AST receipt. Kaplan-Meier survival curves were generated to compare survival among subtypes by AST receipt status, and a semiparametric additive hazard model was used to verify the factors impacting survival outcome., Results: Of 2,214 eligible patients, most (70.8%) were HR+/HER2- followed by HR-/HER2- (14.4%), and 78.6% received guideline-concordant AST. Compared with patients with the HR+/HER2+ subtype, women with other subtypes were more likely to be guideline-concordant after adjusting for sociodemographic and clinical variables. Women with the HR-/HER2+ or HR-/HER2- subtype had a higher risk of any-cause and breast cancer-specific death than those with the HR+/HER2+ subtype. Those who did not receive AST had an additional adjusted hazard of 0.0191 (P=.0001) in overall survival and 0.0126 (P=.0011) in cause-specific survival compared with those who received AST., Conclusions: Most patients received guideline-concordant AST, except for those with the HR+/HER2+ subtype. Patients receiving guideline-adherent adjuvant therapy had better survival outcomes across all breast cancer subtypes.
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- 2019
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19. Racial/ethnic differences in the utilization of chemotherapy among stage I-III breast cancer patients, stratified by subtype: Findings from ten National Program of Cancer Registries states.
- Author
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Zhang L, King J, Wu XC, Hsieh MC, Chen VW, Yu Q, Fontham E, Loch M, Pollack LA, and Ferguson T
- Subjects
- Black or African American, Aged, Aged, 80 and over, Breast Neoplasms classification, Breast Neoplasms epidemiology, Breast Neoplasms ethnology, Delivery of Health Care statistics & numerical data, Ethnicity, Female, Hispanic or Latino, Humans, Middle Aged, United States epidemiology, White People, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Delivery of Health Care ethnology, Receptor, ErbB-2, Registries, Time-to-Treatment statistics & numerical data
- Abstract
Background: The study aimed to examine racial/ethnic differences in chemotherapy utilization by breast cancer subtype., Methods: Data on female non-Hispanic white (NHW), non-Hispanic black (NHB), and Hispanic stage I-III breast cancer patients diagnosed in 2011 were obtained from a project to enhance population-based National Program of Cancer Registry data for Comparative Effectiveness Research. Hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) were used to classify subtypes: HR+/HER2-; HR+/HER2+; HR-/HER2-; and HR-/HER2 + . We used multivariable logistic regression models to examine the association of race/ethnicity with three outcomes: chemotherapy (yes, no), neo-adjuvant chemotherapy (yes, no), and delayed chemotherapy (yes, no). Covariates included patient demographics, tumor characteristics, Charlson Comorbidity Index, other cancer treatment, and participating states/areas., Results: The study included 25,535 patients (72.1% NHW, 13.7% NHB, and 14.2% Hispanics). NHB with HR+/HER2- (adjusted odds ratio [aOR] 1.22, 95% CI 1.04-1.42) and Hispanics with HR-/HER2- (aOR 1.62, 95% CI 1.15-2.28) were more likely to receive chemotherapy than their NHW counterparts. Both NHB and Hispanics were more likely to receive delayed chemotherapy than NHW, and the pattern was consistent across each subtype. No racial/ethnic differences were found in the receipt of neo-adjuvant chemotherapy., Conclusions: Compared to NHW with the same subtype, NHB with HR+/HER2- and Hispanics with HR-/HER2- have higher odds of using chemotherapy; however, they are more likely to receive delayed chemotherapy, regardless of subtype. Whether the increased chemotherapy use among NHB with HR+/HER2- indicates overtreatment needs further investigation. Interventions to improve the timely chemotherapy among NHB and Hispanics are warranted., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
20. The influence of surface functionalization methods on the performance of silicon nanocrystal LEDs.
- Author
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Angı A, Loch M, Sinelnikov R, Veinot JGC, Becherer M, Lugli P, and Rieger B
- Abstract
The influence of silicon nanocrystal (SiNC) surface characteristics obtained from different functionalization methods on the performance of LEDs was investigated. The surface of SiNCs was functionalized with hexyl chains via hydrosilylation (HS) or with organolithium reagents (OLR) and resulting SiNCs were incorporated as the emissive layer in hybrid organic/inorganic LEDs. Devices utilizing SiNCs functionalized with OLR consistently exhibited lower turn-on voltages, higher luminances and external quantum efficiencies compared to those obtained from the HS method. These improvements were attributed to the less dense and monolayer surface coverage of the SiNCs obtained by the OLR method, as well as their higher absolute quantum yield.
- Published
- 2018
- Full Text
- View/download PDF
21. Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.
- Author
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Zhang L, Yu Q, Wu XC, Hsieh MC, Loch M, Chen VW, Fontham E, and Ferguson T
- Subjects
- Adult, Aged, Breast Neoplasms genetics, Breast Neoplasms pathology, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Neoplasm Staging, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms pathology, Breast Neoplasms drug therapy, Receptor, ErbB-2 genetics, Receptors, Estrogen genetics, Receptors, Progesterone genetics, Triple Negative Breast Neoplasms drug therapy
- Abstract
Purpose: To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations., Methods: Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score., Results: Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI < 85% accounted for 30.4 and 27.8%, respectively. Among ER+/PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51)., Conclusions: Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.
- Published
- 2018
- Full Text
- View/download PDF
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